Project Summary/Abstract: Soft-tissue sarcoma (STS) is a recalcitrant group of malignancies with over 50 distinct histologic subtypes. Patient-derived mouse models of the representative STS subtypes that recapitulates disease progression and metastasis optimize the potential for individualizing STS therapy and for discovery of more effective therapeutics. Our laboratory pioneered patient-derived orthotopic xenograft (PDOX) mouse models and has been developing PDOX models of major cancer types for more than 25 years.1-12 PDOX models of colon cancer,1,13 pancreatic cancer,2 lung cancer,3 breast cancer,5 ovarian cancer,4 stomach cancer,6 cervical cancer11 and mesothelioma9 were previously established. In these models, the orthotopic site was determined and metastasis resulted that matched the donor patient.6,11 For the past year, we have focused on establishing a series of mouse models of soft-tissue sarcoma (STS) and have established a series of 25 patient derived STS that represent the most common histologic subtypes, including liposarcoma, leiomyosarcoma, myxofibrosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma (sarcoma not otherwise specified (NOS). In addition we have established several of the more uncommon STS subtypes including follicular dendritic cell sarcoma, extra osseous Ewing?s soft-tissue sarcoma, and extra skeletal chondrosarcoma. The goal of the present application is to determine the correct orthotopic transplantation site for the STS types in order to obtain reliable primary tumor growth and both regional and distant metastasis similar to that seen in patients. The specific aims are as follows: 1) Transplant a series of established STS tumors into different anatomic sites in nude mice, including extremity (muscle), retroperitoneum, peritoneum, and the thoracic cavity, depending on the histotype and site of origin or recurrence. 2) Evaluate the clinical similarity of the outcome of transplant site with respect to primary tumor growth and metastasis. Deliverables: The present application will develop patient-like models of STS sub-types, enabling future personalized therapy and new drug discovery for this recalcitrant disease.